The emerging field of nanoscale infrared (nano-IR) offers label-free molecular contrast, yet its imaging speed is limited by point-by-point traverse acquisition of a three-dimensional (3D) data cube. Here, we develop a spatial-spectral network (SS-Net), a miniaturized deep-learning model, together with compressive sampling to accelerate the nano-IR imaging. The compressive sampling is performed in both the spatial and spectral domains to accelerate the imaging process. The SS-Net is trained to learn the mapping from small nano-IR image patches to the corresponding spectra. With this elaborated mapping strategy, the training can be finished quickly within several minutes using the subsampled data, eliminating the need for a large-labeled dataset of common deep learning methods. We also designed an efficient loss function, which incorporates the image and spectral similarity to enhance the training. We first validate the SS-Net on an open stimulated Raman-scattering dataset; the results exhibit the potential of 10-fold imaging speed improvement with state-of-the-art performance. We then demonstrate the versatility of this approach on atomic force microscopy infrared (AFM-IR) microscopy with 7-fold imaging speed improvement, even on nanoscale Fourier transform infrared (nano-FTIR) microscopy with up to 261.6 folds faster imaging speed. We further showcase the generalization of this method on AFM-force volume-based multiparametric nanoimaging. This method establishes a paradigm for rapid nano-IR imaging, opening new possibilities for cutting-edge research in materials, photonics, and beyond.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the largest single-stranded RNA virus known to date. Its genome contains multiple accessory protein genes that act against host immune responses but are not required for progeny virus production. The functions of the accessory proteins in the viral life cycle have been examined, but their involvement in viral pathogenicity remains unclear. Here, we investigated the roles of the accessory proteins in viral immunopathogenicity. To this end, recombinant SARS-CoV-2 possessing nonsense mutations in the seven accessory protein open reading frames (ORFs) (ORF3a, ORF3b, ORF6, ORF7a, ORF8, ORF9b, and ORF10) was de novo generated using an early pandemic SARS-CoV-2 strain as a backbone. We confirmed that the resultant virus (termed ORF3-10 KO) did not express accessory proteins in infected cells and retained the desired mutations in the viral genome. In cell culture, the ORF3-10 KO virus exhibited similar virus growth kinetics as the parental virus. In hamsters, ORF3-10 KO virus infection resulted in mild weight loss and reduced viral replication in the oral cavity and lung tissue. ORF3-10 KO virus infection led to mild inflammation, indicating that an inability to evade innate immune sensing because of a lack of accessory proteins impairs virus growth in vivo and results in quick elimination from the body. Overall, we showed that SARS-CoV-2 accessory proteins are involved in immunopathogenicity.
BACKGROUND: Although several SARS-CoV-2-related coronaviruses (SC2r-CoVs) were discovered in bats and pangolins, the differences in virological characteristics between SARS-CoV-2 and SC2r-CoVs remain poorly understood. Recently, BANAL-20-236 (B236) was isolated from a rectal swab of Malayan horseshoe bat and was found to lack a furin cleavage site (FCS) in the spike (S) protein. The comparison of its virological characteristics with FCS-deleted SARS-CoV-2 (SC2ΔFCS) has not been conducted yet. METHODS: We prepared human induced pluripotent stem cell (iPSC)-derived airway and lung epithelial cells and colon organoids as human organ-relevant models. B236, SARS-CoV-2, and artificially generated SC2ΔFCS were used for viral experiments. To investigate the pathogenicity of B236 in vivo, we conducted intranasal infection experiments in hamsters. FINDINGS: In human iPSC-derived airway epithelial cells, the growth of B236 was significantly lower than that of the SC2ΔFCS. A fusion assay showed that the B236 and SC2ΔFCS S proteins were less fusogenic than the SARS-CoV-2 S protein. The infection experiment in hamsters showed that B236 was less pathogenic than SARS-CoV-2 and even SC2ΔFCS. Interestingly, in human colon organoids, the growth of B236 was significantly greater than that of SARS-CoV-2. INTERPRETATION: Compared to SARS-CoV-2, we demonstrated that B236 exhibited a tropism toward intestinal cells rather than respiratory cells. Our results are consistent with a previous report showing that B236 is enterotropic in macaques. Altogether, our report strengthens the assumption that SC2r-CoVs in horseshoe bats replicate primarily in the intestinal tissues rather than respiratory tissues. FUNDING: This study was supported in part by AMED ASPIRE (JP23jf0126002, to Keita Matsuno, Kazuo Takayama, and Kei Sato); AMED SCARDA Japan Initiative for World-leading Vaccine Research and Development Centers "UTOPIA" (JP223fa627001, to Kei Sato), AMED SCARDA Program on R&D of new generation vaccine including new modality application (JP223fa727002, to Kei Sato); AMED SCARDA Hokkaido University Institute for Vaccine Research and Development (HU-IVReD) (JP223fa627005h0001, to Takasuke Fukuhara, and Keita Matsuno); AMED Research Program on Emerging and Re-emerging Infectious Diseases (JP21fk0108574, to Hesham Nasser; JP21fk0108493, to Takasuke Fukuhara; JP22fk0108617 to Takasuke Fukuhara; JP22fk0108146, to Kei Sato; JP21fk0108494 to G2P-Japan Consortium, Keita Matsuno, Shinya Tanaka, Terumasa Ikeda, Takasuke Fukuhara, and Kei Sato; JP21fk0108425, to Kazuo Takayama and Kei Sato; JP21fk0108432, to Kazuo Takayama, Takasuke Fukuhara and Kei Sato; JP22fk0108534, Terumasa Ikeda, and Kei Sato; JP22fk0108511, to Yuki Yamamoto, Terumasa Ikeda, Keita Matsuno, Shinya Tanaka, Kazuo Takayama, Takasuke Fukuhara, and Kei Sato; JP22fk0108506, to Kazuo Takayama and Kei Sato); AMED Research Program on HIV/AIDS (JP22fk0410055, to Terumasa Ikeda; and JP22fk0410039, to Kei Sato); AMED Japan Program for Infectious Diseases Research and Infrastructure (JP22wm0125008 to Keita Matsuno); AMED CREST (JP21gm1610005, to Kazuo Takayama; JP22gm1610008, to Takasuke Fukuhara; JST PRESTO (JPMJPR22R1, to Jumpei Ito); JST CREST (JPMJCR20H4, to Kei Sato); JSPS KAKENHI Fund for the Promotion of Joint International Research (International Leading Research) (JP23K20041, to G2P-Japan Consortium, Keita Matsuno, Takasuke Fukuhara and Kei Sato); JST SPRING (JPMJSP2108 to Shigeru Fujita); JSPS KAKENHI Grant-in-Aid for Scientific Research C (22K07103, to Terumasa Ikeda); JSPS KAKENHI Grant-in-Aid for Scientific Research B (21H02736, to Takasuke Fukuhara); JSPS KAKENHI Grant-in-Aid for Early-Career Scientists (22K16375, to Hesham Nasser; 20K15767, to Jumpei Ito); JSPS Core-to-Core Program (A. Advanced Research Networks) (JPJSCCA20190008, to Kei Sato); JSPS Research Fellow DC2 (22J11578, to Keiya Uriu); JSPS Research Fellow DC1 (23KJ0710, to Yusuke Kosugi); JSPS Leading Initiative for Excellent Young Researchers (LEADER) (to Terumasa Ikeda); World-leading Innovative and Smart Education (WISE) Program 1801 from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) (to Naganori Nao); Ministry of Health, Labour and Welfare (MHLW) under grant 23HA2010 (to Naganori Nao and Keita Matsuno); The Cooperative Research Program (Joint Usage/Research Center program) of Institute for Life and Medical Sciences, Kyoto University (to Kei Sato); International Joint Research Project of the Institute of Medical Science, the University of Tokyo (to Terumasa Ikeda and Takasuke Fukuhara); The Tokyo Biochemical Research Foundation (to Kei Sato); Takeda Science Foundation (to Terumasa Ikeda and Takasuke Fukuhara); Mochida Memorial Foundation for Medical and Pharmaceutical Research (to Terumasa Ikeda); The Naito Foundation (to Terumasa Ikeda); Hokuto Foundation for Bioscience (to Tomokazu Tamura); Hirose Foundation (to Tomokazu Tamura); and Mitsubishi Foundation (to Kei Sato).
Dibutyl phthalate (DBP) is a widely-used plasticizer that is dispersed in various environments, causing significant pollution and health risks. The toxic mechanism of DBP has been discussed in recent years, while the susceptibility of mitochondrial DNA (mtDNA) to DBP exposure and the resulting damage remain unclear. In this study, maternal zebrafish were exposed to environmentally relevant concentration of DBP for 0, 2, 4, and 6 weeks. Results showed that DBP exposure impaired health status, leading to the reduced body length and weight, condition factor, hepatosomatic index, and gonadosomatic index. Furthermore, DBP exposure induced oxidative stress and ATP deficiency in the gill and liver in a time-dependent manner. The oxidized mtDNA (ox-mtDNA) levels in the D-loop and ND1 regions were assessed in different tissues, showing distinct response patterns. The high energy-consuming tissues such as heart, brain, gill, and liver exhibited elevated susceptibility to mitochondrial damage, with a rapid increase in ox-mtDNA levels in the short term. Conversely, in muscle, ovary, eggs, and offspring, ox-mtDNA gradually accumulated over the exposure period. Notably, the ox-mtDNA levels in the D-loop region of blood showed a prompt response to DBP exposure, making it convenient for evaluation. Additionally, decreased hatching rates, increased mortality, lipoperoxidation, and depressed swimming performance were observed in offspring following maternal DBP exposure, suggesting the inherited impairments of maternal mtDNA. These findings highlight the potential for ox-mtDNA to serve as a convenient biomarker for environmental contamination, aiding in ecological risk assessment and forewarning systems in aquatic environment.
Notoginseng leaf triterpenes (PNGL), derived from the dried stems and leaves of P. notoginseng, is a phytoestrogen that exerts many neuroprotective effects in vivo and in vitro of ischemic stroke. However, its impact on neurological restoration specifically in relation to angiogenesis following ischemic stroke remains unexplored. The aim of this study was to assess the effects of PNGL on angiogenesis subsequent to ischemic stroke. Male Sprague-Dawley rats were utilized in this study and were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). Post-ischemia, PNGL were administered through intraperitoneal (i.p.) injection. The high-performance liquid chromatography (HPLC) fingerprinting, triphenyltetrazolium chloride (TTC) staining, immunofluorescent staining, network pharmacology and western blot analyses were assessed to determine the therapeutical effect and molecular mechanisms of PNGL on cerebral ischemia/reperfusion injury. Our findings demonstrate that PNGL effectively reduced infarct volume, enhanced cerebral blood flow, and induced angiogenesis in rats subjected to MCAO/R. Notably, PNGL also facilitated neuronal proliferation and migration in HUMECs in vitro. The proangiogenic effects of PNGL were found to be linked to the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and the AMPK/SIRT1-mediated PGC-1/ERα axis, as well as the activation of neurological function. Our study provides evidence that PNGL hold promise as an active ingredient of inducing proangiogenic effects, potentially through the activation of the Nrf2 pathway and the AMPK/SIRT1-mediated PGC-1/ERα axis. These findings contribute to the understanding of novel mechanisms involved in the restoration of neurological function following PNGL treatment for ischemic stroke.
BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a common chronic disease, and its aetiology and pathogenesis remain unclear. This study aimed to identify potential urine and serum biomarkers in patients with IC/BPS to further understand the pathogenesis and diagnosis of the disease. METHODS: Patients with IC/BPS diagnosed and treated in the First Hospital of Hebei Medical University from 1 July 2021 to 30 July 2023 were selected. The urine and serum biomarkers of 50 patients with IC/BPS were investigated and compared with the urine and serum samples of 50 healthy controls. IBM SPSS Statistics 26.0 was used for statistical analysis of the recorded data by using chi-square test, T-test and logistic regression analysis. RESULTS: Overall, 50 patients with IC/BPS (mean age, 54.20 ± 8.15 years) were included in the study. Those with history of urinary diseases, anxiety or depression were susceptible to IC/BPS. Levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), nerve growth factor, and prostaglandin E2 (PGE2) in urine, as well as IL-8, TNF-α, and PGE2 in serum, were found to significantly increase in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). These differences were statistically significant (p < 0.05). Multifactor analysis showed that anxiety, depression, IL-6, IL-8, TNF-α and PEG2 are risk factors for patients with IC/BPS. CONCLUSIONS: Multiple biomarkers were identified in the urine and serum of patients with IC/BPS, suggesting a potential close relationship to the pathogenesis of IC/BPS.
Biomarkers , Cystitis, Interstitial , Humans , Cystitis, Interstitial/blood , Cystitis, Interstitial/urine , Biomarkers/blood , Biomarkers/urine , Middle Aged , Female , Male , Adult , Tumor Necrosis Factor-alpha/blood , Interleukin-6/blood , Interleukin-6/urine
Metal-organic frameworks (MOFs) are limited by small pores and buried active sites, and their enzyme-like catalytic activity is still very low. Herein, laccase was employed as the organic component to construct laccase@Cu3(BTC)2 nanofractal microspheres. During the preparation process, laccase adsorbed Cu2+ by electrostatic attractive interaction, then combined with Cu2+ by coordination interaction, and finally induced the in situ growth of H3BTC2 in multiple directions by electrostatic repulsion. Interestingly, electrostatic repulsion was tuned efficiently by adjusting the Cu2+ concentration to obtain laccase@Cu3(BTC)2 nanofractal microspheres (nanosheet microspheres, nanorod microspheres, and nanoneedle microspheres). Laccase@Cu3(BTC)2 nanorod microspheres exhibited the highest catalytic efficiency, which was 14-fold higher than that of smooth microspheres. The mechanism of the improvement of catalytic activity in the degradation of BPA was proposed for the first time. The enhanced catalytic activity depended on the adsorption effect of the nanorod framework and dual cycle synergistic catalysis of Cu+/Cu2+ active sites, which accelerated substrate diffusion and electron transfer. The catalytic mechanism of enzyme@MOF nanofractal microspheres not only deepens our understanding of enzyme and MOF synergistic catalysis but also provides new insights into the design of catalysts.
Cell cycle exit and neuronal differentiation 1 (CEND1), highly expressed in the brain, is a specific transmembrane protein which plays a tumor suppressor role. This study is performed to investigate the role of CEND1 in various cancers through pan-cancer analysis, and further investigate its functions in gliomas by cell experiments. The expression and subcellular localization of CEND1 in different cancer types were analyzed utilizing the data from the GEPIA, UCSC, UALCAN and HPA databases. Relationships of CEND1 expression with prognosis, immunomodulation-related genes, immune checkpoint genes, microsatellite instability (MSI), tumor mutation burden (TMB) and RNA modifications were analyzed based on the TCGA database. The ESTIMATE algorithm was utilized to evaluate tumors' StromalScore, Immune Score, and ESTIMATES Score. The cBioPortal database was employed to analyze the categories and frequencies of CEND1 gene alterations. Biological functions and co-expression patterns of CEND1 in gliomas were explored using the LinkedOmics database, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted. The interactions between CEND1 and drugs were explored employing the Comparative Toxicogenomics Database and molecular docking technology. Cell experiments were conducted to analyze triptonide's effects on glioma cells through CCK-8, flow cytometry and qRT-PCR. CEND1 was lowly expressed in gliomas, and high CEND1 expression was correlated to better overall survival of glioma patients (HR = 0.65, P = 0.02). Deep deletion was the main type of hereditary change of CEND1 mutation. CEND1 expression was markedly associated with immune infiltration, TMB, MSI, and RNA modification in various tumors (r > 0.3, P < 0.05). CEND1 co-expressed genes in gliomas were markedly correlated with immune responses and cell cycle (FDR < 0.05). Triptonide could bind well to CEND1 (-5.0 kcal/mol), and triptonide could facilitate CEND1 expression in glioma cells and cell apoptosis, and block the cell cycle progression (P < 0.05). CEND1 serves as a potential biomarker for pan-cancer. Particularly in gliomas, CEND1 is a key regulator of cell apoptosis and cell cycle, and a potential target for glioma treatment.
Introduction: Numerous studies show that microbes in the human body are very closely linked to the human host and can affect the human host by modulating the efficacy and toxicity of drugs. However, discovering potential microbe-drug associations through traditional wet labs is expensive and time-consuming, hence, it is important and necessary to develop effective computational models to detect possible microbe-drug associations. Methods: In this manuscript, we proposed a new prediction model named LCASPMDA by combining the learnable graph convolutional attention network and the self-paced iterative sampling ensemble strategy to infer latent microbe-drug associations. In LCASPMDA, we first constructed a heterogeneous network based on newly downloaded known microbe-drug associations. Then, we adopted the learnable graph convolutional attention network to learn the hidden features of nodes in the heterogeneous network. After that, we utilized the self-paced iterative sampling ensemble strategy to select the most informative negative samples to train the Multi-Layer Perceptron classifier and put the newly-extracted hidden features into the trained MLP classifier to infer possible microbe-drug associations. Results and discussion: Intensive experimental results on two different public databases including the MDAD and the aBiofilm showed that LCASPMDA could achieve better performance than state-of-the-art baseline methods in microbe-drug association prediction.
Objective: To investigate the risk factors for the development of mild cognitive dysfunction in hypertensive patients in the community and to develop a risk prediction model. Method: The data used in this study were obtained from two sources: the China Health and Retirement Longitudinal Study (CHARLS) and the Chinese Longitudinal Healthy Longevity Survey (CLHLS). A total of 1121 participants from CHARLS were randomly allocated into a training set and a validation set, following a 70:30 ratio. Meanwhile, an additional 4016 participants from CLHLS were employed for external validation of the model. The patients in this study were divided into two groups: those with mild cognitive impairment and those without. General information, employment status, pension, health insurance, and presence of depressive symptoms were compared between the two groups. LASSO regression analysis was employed to identify the most predictive variables for the model, utilizing 14-fold cross-validation. The risk prediction model for cognitive impairment in hypertensive populations was developed using generalized linear models. The model's discriminatory power was evaluated through the area under the receiver operating characteristic (ROC) curve and calibration curves. Results: In the modeling group, eight variables such as gender, age, residence, education, alcohol use, depression, employment status, and health insurance were ultimately selected from an initial pool of 21 potential predictors to construct the risk prediction model. The area under the curve (AUC) values for the training, internal, and external validation sets were 0.777, 0.785, and 0.782, respectively. All exceeded the threshold of 0.7, suggesting that the model effectively predicts the incidence of mild cognitive dysfunction in community-based hypertensive patients. A risk prediction model was developed using a generalized linear model in conjunction with Lasso regression. The model's performance was evaluated using the area under the receiver operating characteristic (ROC) curve. Hosmer-Lemeshow test values yielded p = .346 and p = .626, both of which exceeded the 0.05 threshold. Calibration curves demonstrated a significant agreement between the nomogram model and observed outcomes, serving as an effective tool for evaluating the model's predictive performance. Discussion: The predictive model developed in this study serves as a promising and efficient tool for evaluating cognitive impairment in hypertensive patients, aiding community healthcare workers in identifying at-risk populations.
The pathogenesis of ferroptosis in traumatic brain injury (TBI) is unclear; therefore, we aimed to identify key molecules associated with ferroptosis in TBI using bioinformatics analysis to determine its underlying mechanisms. GSE128543 dataset was downloaded from the Gene Expression Omnibus (GEO) database, and TBI-associated modules were obtained by weighted gene co-expression network analysis (WGCNA). We identified 60 differentially expressed genes (DEGs) by intersecting the modules with ferroptosis and glycolysis/gluconeogenesis gene libraries. The hypoxia-inducible factor-1 (HIF-1) signaling pathway was identified to be critical for ferroptosis post-TBI, and protein-protein interaction (PPI) network identified 20 hub genes, including phosphoglycerate kinase 1 (PGK1), ribosomal protein (RP) family, pyruvate kinase M1/2 (PKM), hypoxia-inducible factor 1α subunit (HIF-1α), and MYC genes. In this study, we further explored the role of PGK1, a gene involved in HIF-1 signaling pathway; however, its role and mechanism in TBI are still unclear. Moreover, we constructed a TBI mouse model and examined PGK1 and HIF-1α expression levels, and the results revealed their expressions increased after cortical injury in mice and they co-localized in the same cells. Furthermore, we examined the expressions of PGK1 in the cerebrospinal fluid of 20 clinical patients with different degrees of brain injuries within 48 h of surgery and examined the cognitive function of patients according to the Glasgow Coma Scale (GCS). The results revealed that PGK1 expression level was negatively correlated with the severity of the brain injury. These findings suggest that PGK1 may become a potential hub gene for ferroptosis via the HIF-1 signaling pathway, second to neurological injury after TBI, thereby affecting patient prognosis.
Inspired by the imbalance between extrinsic and intrinsic tendon healing, this study fabricated a new biofilter scaffold with a hierarchical structure based on a melt electrowriting technique. The outer multilayered fibrous structure with connected porous characteristics provides a novel passageway for vascularization and isolates the penetration of scar fibers, which can be referred to as a biofilter process. In vitro experiments found that the porous architecture in the outer layer can effectively prevent cell infiltration, whereas the aligned fibers in the inner layer can promote cell recruitment and growth, as well as the expression of tendon-associated proteins in a simulated friction condition. It was shown in vivo that the biofilter process could promote tendon healing and reduce scar invasion. Herein, this novel strategy indicates great potential to design new biomaterials for balancing extrinsic and intrinsic healing and realizing scarless tendon healing.
Radiation-induced intestinal injury is the most common side effect during radiotherapy of abdominal or pelvic solid tumors, significantly impacting patients' quality of life and even resulting in poor prognosis. Until now, oral application of conventional formulations for intestinal radioprotection remains challenging with no preferred method available to mitigate radiation toxicity in small intestine. Our previous study revealed that nanomaterials derived from spore coat of probiotics exhibit superior anti-inflammatory effect and even prevent the progression of cancer. The aim of this work is to determine the radioprotective effect of spore coat (denoted as spore ghosts, SGs) from three clinically approved probiotics (B.coagulans, B.subtilis and B.licheniformis). All the three SGs exhibit outstanding reactive oxygen species (ROS) scavenging ability and excellent anti-inflammatory effect. Moreover, these SGs can reverse the balance of intestinal flora by inhibiting harmful bacteria and increasing the abundance of Lactobacillus. Consequently, administration of SGs significantly reduce radiation-induced intestinal injury by alleviating diarrhea, preventing X-ray induced apoptosis of small intestinal epithelial cells and promoting restoration of barrier integrity in a prophylactic study. Notably, SGs markedly improve weight gain and survival of mice received total abdominal X-ray radiation. This work may provide promising radioprotectants for efficiently attenuating radiation-induced gastrointestinal syndrome and promote the development of new intestinal predilection.
Probiotics , Radiation-Protective Agents , Spores, Bacterial , Animals , Probiotics/pharmacology , Mice , Administration, Oral , Radiation-Protective Agents/pharmacology , Radiation-Protective Agents/therapeutic use , Radiation-Protective Agents/chemistry , Spores, Bacterial/radiation effects , Radiation Injuries/drug therapy , Reactive Oxygen Species/metabolism , Intestine, Small/microbiology , Intestine, Small/radiation effects , Intestine, Small/pathology , Humans , Apoptosis/drug effects , Male , Gastrointestinal Microbiome/drug effects , Intestines/radiation effects , Intestines/microbiology , Intestines/pathology , Radiation Injuries, Experimental/pathology
Comprehending the catalyst structural evolution during the electrocatalytic process is crucial for establishing robust structure/performance correlations for future catalysts design. Herein, we interrogate the structural evolution of a promising Cu-Ag oxide catalyst precursor during electrochemical carbon monoxide reduction. By using extensive in situ and ex situ characterization techniques, we reveal that the homogenous oxide precursors undergo a transformation to a bimetallic composite consisting of small Ag nanoparticles enveloped by thin layers of amorphous Cu. We believe that the amorphous Cu layer with undercoordinated nature is responsible for the enhanced catalytic performance of the current catalyst composite. By tuning the Cu/Ag ratio in the oxide precursor, we find that increasing the Ag concentration greatly promotes liquid products formation while suppressing the byproduct hydrogen. CO2/CO co-feeding electrolysis and isotopic labelling experiments suggest that high CO concentrations in the feed favor the formation of multi-carbon products. Overall, we anticipate the insights obtained for Cu-Ag bimetallic systems for CO electroreduction in this study may guide future catalyst design with improved performance.
In this study, a UV-driven photocatalytic activation of peroxymonosulfate (PMS) system was constructed using bimetallic metal-organic frameworks to degrade pharmaceuticals and personal care products (PPCPs). Mn-MIL-53(Fe) was successfully synthesised by adjusting the doping ratio of Mn using solvothermal method. The removal of ibuprofen (IBP) by UV/Mn-MIL-53(Fe)/PMS process was as high as 79.7% in 30 min with a Mn doping ratio of 1.0 (molar ratio of Mn to Fe), and the reaction rate constant was 26.9% higher than undoped. Mn-MIL-53(Fe) had been systematically characterized in terms of its physical structure, microscopic morphology, surface functional groups and photoelectric properties. The mechanism investigation revealed that the cycling of Mn and Fe accelerated the rate of electron transfer in the system, which significantly increased the activation efficacy of PMS to generate more hydroxyl and sulfate radicals for IBP degradation. A total of 13 transformation products were detected during the degradation of IBP by the UV/Mn-MIL-53(Fe)/PMS process. Theoretical calculations were used to predict the sites on the IBP molecule that were vulnerable to attack, and four possible degradation pathways were deduced. The excellent stability and efficient catalytic properties of Mn-MIL-53(Fe) provided a promising solution to the problem of water treatment contaminated with PPCPs.
Ionic liquids (ILs) become emerging environmental pollutants. Especially, alkyl imidazolium ILs commonly showed stimulation in toxicological studies and mechanisms remained to be explored. In the present study, alkyl imidazolium tetrafluoroborate ([amim]BF4), with ethyl ([emim]), hexyl ([hmim]) and octyl ([omim]) as side-chains, were chosen as target ILs. Their toxicities on the reproduction and lifespan of Caenorhabditis elegans were explored with two types (A and B) exposure arrangements to mimic realistic intermittent multi-generational exposure scenarios. In type A scenario, there was an exposure every 4 generations with 12 generations in total, and in type B one, there was an exposure every two generations with 12 generations in total. Result showed that [emim]BF4 caused inhibition on the reproduction in 8 generations in type A exposure but 6 ones in type B exposure. Meanwhile, [hmim]BF4 showed inhibition in one generation and stimulation in 3 generations in type A exposure, but stimulation in 6 generations in type B exposure. Also, [omim]BF4 showed stimulation in one generation in type B exposure. Collectively, the results demonstrated less frequencies of inhibition, or more frequencies of stimulation, in the exposure scenario with more frequent exposures. Further mechanism exploration was performed to measure the lipid storage and metabolism in the aspect of energy supply. Results showed that [emim]BF4, [hmim]BF4 and [omim]BF4 commonly stimulated the triglyceride (TG) levels across generations. They also disturbed the activities of glycerol-3-phosphate acyltransferase (GPAT) and acetyl CoA carboxylase (ACC) in lipogenesis, those of adipose triglyceride lipase (ATGL) and carnitine acyl transferase (CPT) in lipolysis, and also the contents of acetyl-CoA (ACA). Further data analysis indicated the energy allocation among life traits including reproduction, antioxidant responses and hormone regulations.
Inherently chiral calix[4]arenes are an excellent structural scaffold for asymmetric synthesis, chiral recognition, sensing, and circularly polarized luminescence. However, their catalytic asymmetric synthesis remains challenging. Herein, we report an efficient synthesis of inherently chiral calix[4]arene derivatives via cascade asymmetric cyclization and oxidation reactions. The three-component reaction features a broad substrate scope (33 examples), high efficiency (up to 90% yield), and excellent enantioselectivity (>95% ee on average). The potential applications of calix[4]arene derivatives are highlighted by their synthetic transformation and a detailed investigation of their photophysical and chiroptical properties.
BACKGROUND: Ruminant gut microbiota are critical in ecological adaptation, evolution, and nutrition utilization because it regulates energy metabolism, promotes nutrient absorption, and improves immune function. To study the functional roles of key gut microbiota in sheep and goats, it is essential to construct reference microbial gene catalogs and high-quality microbial genomes database. RESULTS: A total of 320 fecal samples were collected from 21 different sheep and goat breeds, originating from 32 distinct farms. Metagenomic deep sequencing and binning assembly were utilized to construct a comprehensive microbial genome information database for the gut microbiota. We successfully generated the largest reference gene catalogs for gut microbiota in sheep and goats, containing over 162 million and 82 million nonredundant predicted genes, respectively, with 49 million shared nonredundant predicted genes and 1138 shared species. We found that the rearing environment has a greater impact on microbial composition and function than the host's species effect. Through subsequent assembly, we obtained 5810 medium- and high-quality metagenome-assembled genomes (MAGs), out of which 2661 were yet unidentified species. Among these MAGs, we identified 91 bacterial taxa that specifically colonize the sheep gut, which encode polysaccharide utilization loci for glycan and mucin degradation. CONCLUSIONS: By shedding light on the co-symbiotic microbial communities in the gut of small ruminants, our study significantly enhances the understanding of their nutrient degradation and disease susceptibility. Our findings emphasize the vast potential of untapped resources in functional bacterial species within ruminants, further expanding our knowledge of how the ruminant gut microbiota recognizes and processes glycan and mucins. Video Abstract.
Bacteria , Feces , Gastrointestinal Microbiome , Goats , Mucins , Polysaccharides , Animals , Goats/microbiology , Sheep/microbiology , Mucins/metabolism , Polysaccharides/metabolism , Bacteria/classification , Bacteria/genetics , Bacteria/metabolism , Feces/microbiology , Metagenome , Genome, Bacterial , Metagenomics/methods , Phylogeny , High-Throughput Nucleotide Sequencing
OBJECTIVE: To develop and evaluate a nomogram prediction model for the 3-month mortality risk of patients with sepsis-associated acute kidney injury (S-AKI). METHODS: Based on the American Medical Information Mart for Intensive Care- IV (MIMIC- IV), clinical data of S-AKI patients from 2008 to 2021 were collected. Initially, 58 relevant predictive factors were included, with all-cause mortality within 3 months as the outcome event. The data were divided into training and testing sets at a 7 : 3 ratio. In the training set, univariate Logistic regression analysis was used for preliminary variable screening. Multicollinearity analysis, Lasso regression, and random forest algorithm were employed for variable selection, combined with the clinical application value of variables, to establish a multivariable Logistic regression model, visualized using a nomogram. In the testing set, the predictive value of the model was evaluated through internal validation. The receiver operator characteristic curve (ROC curve) was drawn, and the area under the curve (AUC) was calculated to evaluate the discrimination of nomogram model and Oxford acute severity of illness score (OASIS), sequential organ failure assessment (SOFA), and systemic inflammatory response syndrome score (SIRS). The calibration curve was used to evaluate the calibration, and decision curve analysis (DCA) was performed to assess the net benefit at different probability thresholds. RESULTS: Based on the survival status at 3 months after diagnosis, patients were divided into 7 768 (68.54%) survivors and 3 566 (31.46%) death. In the training set, after multiple screenings, 7 variables were finally included in the nomogram model: Logistic organ dysfunction system (LODS), Charlson comorbidity index, urine output, international normalized ratio (INR), respiratory support mode, blood urea nitrogen, and age. Internal validation in the testing set showed that the AUC of nomogram model was 0.81 [95% confidence interval (95%CI) was 0.80-0.82], higher than the OASIS score's 0.70 (95%CI was 0.69-0.71) and significantly higher than the SOFA score's 0.57 (95%CI was 0.56-0.58) and SIRS score's 0.56 (95%CI was 0.55-0.57), indicating good discrimination. The calibration curve demonstrated that the nomogram model's calibration was better than the OASIS, SOFA, and SIRS scores. The DCA curve suggested that the nomogram model's clinical net benefit was better than the OASIS, SOFA, and SIRS scores at different probability thresholds. CONCLUSIONS: A nomogram prediction model for the 3-month mortality risk of S-AKI patients, based on clinical big data from MIMIC- IV and including seven variables, demonstrates good discriminative ability and calibration, providing an effective new tool for assessing the prognosis of S-AKI patients.
Acute Kidney Injury , Nomograms , Organ Dysfunction Scores , Sepsis , Humans , Acute Kidney Injury/diagnosis , Acute Kidney Injury/mortality , Acute Kidney Injury/etiology , Sepsis/mortality , Sepsis/diagnosis , Sepsis/complications , Prognosis , Logistic Models , Risk Factors , ROC Curve , Female , Male , Middle Aged , Severity of Illness Index , Risk Assessment/methods
